Exposure of individuals to foreign antigens, such as those associated with bacteria and viruses, results in production of thousands of different antibody molecules. My laboratory is interested in how organisms develop such a large and diverse array of antibodies during an immune response. The goals of our research are to elucidate the molecular genetic mechanisms that generate antibody diversity and that regulate the expression of immunoglobulin (lg) genes
Mammals use several strategies to generate antibody diversity. They have the capacity to produce many different Ig heavy chains and light chains (the building blocks of antibody molecules), which can be used in different combinations to generate antibody diversity. The Ig heavy and light chains each have variable (V) regions and constant regions that are encoded by separate genes. Different V genes, of which there are hundreds, are used to produce antibodies of different specificities. Rearrangement of the V genes by somatic recombination is required before an antibody can be produced by a B lymphocyte. Additional diversity is generated in gut-associated lymphoid tissues, and exposure to microbial flora of the gut is required for this somatic diversification to occur. We are investigating how a lymphocyte chooses to rearrange and express a particular V gene, how this rearranged V gene undergoes somatic diversification, and how intestinal microorganisms mediate somatic diversification oft heV genes. Details of individual projects can be found at our laboratory home page.
For our investigations we use normal and transgenic rabbits as well as rabbits genetically modified by nuclear transfer techniques. We use molecular genetic, immunochemical, and cell culture techniques, including DNA cloning and sequencing and in vitro gene expression.
Siewe, B.T., Kalis, S., Esteves, P. J., Zhou, T., and Knight, K. L. (2010) A novel functional rabbit IL-7 isoform. Developmental and Comparative Immunology, 34:828-36.
Yeramilli, V.A. and Knight, K. L. (2010) Requirement for BAFF and APRIL during B cell development in GALT., J. Immunology, 184:5527-36.Severson, K.M., Mallozzi, M., Driks, A., and Knight, K.L. (2010) B cell development in GALT: Role of bacterial and endogenous superantigen-like molecules, J. Immunology, 184:6782 – 6789.
Severson, K.M., Mallozzi, M., Bozue, J., Welkos, S, Cote, C.K., Knight, K.L., and Driks, (2009) A., Roles of the Bacillus anthracis Spore Protein ExsK in Exosporium Maturation and Germination. J. Bacteriology, 191:7587-7596.
Lanning, D.K., Severson, K.M., and Knight, K.L. (2008) Intestinal Bacteria: Mucosal Tissue Development and Gut Homeostasis, in Immunity against Mucosal Pathogens, Vajdy, M. ed., Springer Publ. pp. 135-150.
Jasper, P. J., Rhee, K. J., Kalis, S. L., Sethupathi, P., Yam P. C., Zhai, S. K., Knight, K. L. B lymphocyte deficiency in IgH-transgenic rabbits. Eur J Immunol. 2007 Jul 12;37(8):2290-2299.
Kalis, S. L., Zhai, S.K., Yam, P. C, Witte, P. L., Knight, K. L. Suppression of B lymphopoiesis at a lymphoid progenitor stage in adult rabbits. Int. Immunol. 2007 Jun;19(6):801-11.
Rhee, K.-J., Jasper, P.J., Sethupathi, P., Shanmugam, M., Lanning D. and Knight, K.L.: (2005) Positive selection of the peripheral B cell repertoire in gut associated lymphoid tissue. J. Exptl. Med. 201: 55-62.
Volgina, V., Yam, P. C., and Knight, K.L.: (2005) A negative regulatory elementin the rabbit 3'IgH chromosomal region. International Immunology, 17:973-982
Shanmugam, M., Sethupathi, P., Rhee, K.-J., Yong, S., and Knight, K.L. (2005) Bacterial-induced Inflammation in Germ-free Rabbit Appendix. Inflammatory Bowel Diseases. 11:992-996.
Lanning, D.K., Rhee, K.-J., and Knight, K.L.: (2005) Intestinal Bacteria and Development of the B lymphocyte Repertoire, Trends in Immunology, 26:419
Mage, R.G., Lanning, D., and Knight, K.L.: (2005) B Cell and Antibody Repertoire Development in Rabbits: the Requirement of Gut-Associated Lymphoid Tissues, Development and Comparative Immunology. 30:137-153.
Jasper, P.J., Rhee, K.-J., Kalis, S.L., Sethupathi, P., Yam, P.-C., Zhai, S.-K., and Knight, K.L.: (2005) B Lymphocyte Deficiency in IgH Transgenic Rabbits,submitted.
Rhee, K.-J., Sethupathi, P., Driks, A., Lanning, D.K., Knight, K.L.: (2004) Role of Commensal Bacteria in Development of Gut-Associated Lymphoid Tissues and Preimmune Antibody Repertoire. J. Immunology, 172:1118.
Esteves, P.J., Lanning, D., Ferrand, N., Knight, K. L., Zhai, S.-K. and van der Loo, W.: (2004) Allelic variation at the VHa locus in natural populations of rabbit (Oryctolagus cuniculus, L.), J. Immunology, 172:1044.
Lanning, D., Osborne, B.A. and Knight, K.L.: (2004) Immunoglobulin Genes and Generation of Antibody Repertoires in Higher Vertebrates: A Key Role for GALT, in Molecular Biology of B cells, edited by F.W. Alt, T. Honjo and M.S. Neuberger, Elsevier Science Ltd., 433-448.